Description of the Related Art
The taxane family of terpenes has received much attention in the scientific and medical community, because members of this family have demonstrated broad spectrum anti-leukemic and tumor-inhibitory activity. A well-known member of this family is paclitaxel (1, Taxol®).

Paclitaxel was first isolated from the bark of the pacific yew tree (Taxus brevifolia) in 1971, and has proved to be a potent natural anti-cancer agent. To date, paclitaxel has been found to have activity against different forms of leukemia and against solid tumors in the breast, ovary, brain, and lung in humans.
As will be appreciated, this beneficial activity has stimulated an intense research effort over recent years with a view to identifying other taxanes having similar or improved properties, and with a view to developing synthetic pathways for making these taxanes, such as paclitaxel.
This research effort led to the discovery of a synthetic analog of paclitaxel, namely, docetaxel (2, more commonly known as taxotere). As disclosed in U.S. Pat. No. 4,814,470, taxotere has been found to have a very good anti-tumor activity and better bio-availability than paclitaxel. Taxotere is similar in structure to paclitaxel, having t-butoxycarbonyl instead of benzoyl on the amino group at the 3′ position, and a hydroxy group instead of the acetoxy group at the C-10 position.

As will be appreciated, taxanes are structurally complicated molecules, and the development of commercially viable synthetic methods to make taxanes has been a challenge. A number of semi-synthetic pathways have been developed over the years, which typically begin with the isolation and purification of a naturally occurring starting material, which can be converted to a specific taxane derivative of interest. For example, paclitaxel and docetaxel may be prepared semi-synthetically from 10-deacetylbaccatin III or baccatin III as set forth in U.S. Pat. No. 4,924,011 (Denis et al.) and U.S. Pat. No. 4,924,012 (Colin et al.), or by the reaction of a beta-lactam and a suitably protected 10-deacetylbaccatin III or baccatin III derivative as set forth in U.S. Pat. No. 5,175,315 (Holton et al.) or U.S. patent application Ser. No. 10/683,865, which application is assigned to the assignee of the present invention.
Another important taxane derivative is Canadensol (2.1) and its derivatives. These can be prepared as described in U.S. Pat. No. 6,410,756 B1 (Zamir et al.).

The precursors or starting material, 10-deacetylbaccatin III (10-DAB, 3) and baccatin III (BACC III, 4) can be separated from mixtures extracted from natural sources such as the needles, stems, bark or heartwood of numerous Taxus species and have the following structures:

Although much of the research towards the semi-synthesis of paclitaxel and taxotere has involved the use of 10-deacetylbaccatin III as the starting material, other taxanes from the Taxus species, such as 9-dihydro-13-acetylbaccatin III (9-DHB, 5), present in the Canadian yew (Taxus Canadensis), cephalomannine (6), 10-deacetyl taxol (10-DAT, 7), 7-xylosyl taxol (8), 10-deacetyl-7-xylosyl taxol (9) and a number of 7-epi-taxanes can also be utilised as suitable starting materials, that is, due to their availability from natural sources.

In addition, U.S. Pat. Nos. 5,202,448 and 5,256,801 (Carver et al.), U.S. Pat. No. 5,449,790 (Zheng et al.) and U.S. Pat. No. 6,281,368 (McChesney et al.) disclose processes for converting certain taxanes (namely, paclitaxel, cephalomannine, 10-deacetyl taxol and certain 10-deacetyl taxol derivatives) present in partially purified taxane mixtures into 10-deacetylbaccatin III and baccatin III, which may be subsequently utilised in the foregoing semi-synthetic pathways.
As identified above, U.S. Pat. No. 4,924,011 by Denis et al. discloses a semi-synthetic process for producing paclitaxel using either baccatin III or 10-deacetylbaccatin III as a starting material. The disadvantage of the reaction process scheme advanced by Denis is it includes a long reaction pathway, it involves a complex procedure and ultimately, the yield of the protected taxane, namely, the taxane intermediate is low (only 40% in the form of a mixture of two epimers in the ratio of 60:40).
Although there have been many advances in the field, there remains a need for new and improved processes for the preparation of taxane derivatives and their conversion to paclitaxel, docetaxel, canadensol and its derivatives, and also for the preparation of taxane intermediates from crude and partially purified mixtures comprising a plurality of taxanes. It is the aim of the present invention to at least address some of the problems outlined above.